Lactic acid bacteria found in Korean traditional fermented food, e.g., kimchi, inhabit the digestive system of a human body and decompose fibrous materials and complex proteins into important nutrients. Viable microorganisms like lactic acid bacteria are beneficial to gastrointestinal tracts of hosts such as animals including humans due to them improving intestinal microorganism environments of the hosts and are referred to as probiotics. Probiotics are required to have excellent acid resistance and bile resistance, and strong adhesion to intestinal epithelial cells since they need to be orally administered, reach the small intestine and adhere to the surface of the small intestine in order to be effective as probiotics.
Lactobacillus sp. lactic acid bacteria are probiotics widely found in Korean traditional fermented food such as Kimchi. Lactobacillus sp. microorganisms produce lactic acid under homo-fermentation or hetero-fermentation and are widely found in intestinal tracts of animals including humans, and in fermentation of dairy products and vegetables. Lactobacillus sp. microorganisms maintain an acidic pH balance to suppress propagation of hazardous bacteria such as E. coli or Clostridium and relieve diarrhea and constipation. Lactobacillus sp. microorganisms also synthesize vitamins, have anti-cancer activities, and reduce serum cholesterol. Acidophillin produced by lactobacillus is known to inhibit the growth of shigella, salmonella, staphylococcus, E. coli, or the like. Acidophillin also suppresses the propagation of causative microorganisms of diarrhea and normalizes intestinal flora to prevent diarrhea (Michael and Philippe, Probiotics and prebiotics: Effects on diarrhea, The journal of nutrition, Volume 137, March 2007, pages 803S-811S; Roberfroid, Prebiotics and probiotics: Are they functional foods?, American journal of clinical nutrition, Volume 71, June 2000, pages 1682S-1687S).
Based on the Lactobacillus sp. microorganism's functions as stated above, research into Lactobacillus sp. microorganism as probiotics and livestock feed is being vigorously conducted. Bacterial diarrhea in livestock causes mortality and a reduction in the rate of weight gain. Thus, a method of adding antibiotics to livestock feed has been widely used in order to prevent bacterial diarrhea and increase the productivity of livestock. However, due to the appearance of antibiotic resistant bacteria and remaining antibiotics in the livestock, the use of antibiotics has been limited and organic methods of raising livestock have been recommended (Korean Patent Publication No. 1998-78358)(McEwen and Fedorka-Cray, Antimicrobial use and resistance in animals, Clinical infectious Diseases, Volume 34, June 2002, pages S93-S106).
In addition, lactic acid bacteria such as Lactobacillus sp. microorganism are known to have immune response-enhancing effects. As such, research on the mechanism of effects of lactic acid bacteria on immune response-enhancing effects has been conducted. Even though specific mechanisms have not yet been revealed, it is known that lactic acid bacteria are orally administered and inhabit the intestines to influence the intestinal immune system. For example, the intake of lactic acid bacteria via yogurt is known to increase antibiotic activities of lymphocytes of Peyer's patches. Lactic acid bacteria are known to enhance IgA response according to research into animals and humans. In addition, the immune system representing resistance in the body against external microbial pathogens is divided into innate immunity and adaptive immunity, both of which are influenced by lactic acid bacteria. According to the innate immunity of the intestinal immune system, the lactic acid bacteria are known to prevent and kill pathogens thereby having a function of maintaining healthy conditions against infection. Innate immune reaction plays an important role in suppressing the increase of the number of external pathogens at an early stage of an infection. Additionally, innate immune reaction delivers antigens and co-stimulatory molecules, thereby inducing the activation of the adaptive immunity subsequent to the innate immune system. Representative immunocytes related to the innate immune reaction includes NK cells, neutrophiles, macrophages, and dendritic cells (Fearon D T, Locksley R M, Science 1996, 272:50-53, The instructive role of innate immunity in the acquired immune response). Adaptive immunity substantially induces the removal of external pathogen when a subject is infected, and the immunocytes corresponding to adaptive immunity include T lymphocytes and B lymphocytes. Accordingly, physical resistance to external pathogens may depend on the enhancement of the activity of adaptive immunity (Gowans J L., Immunology Today. 1996 June; 17(6):288-91, The lymphocyte—a disgraceful gap in medical knowledge).
According to the adaptive immunity, macrophages that decompose antigens to bring them into contact with T lymphocytes are activated to increase the production of a variety of cytokines, particularly, interleukin, IL-12, and IL-18. In this regard, some components of the cell walls of lactic acid bacteria activate NF-κB and STAT signal transfers in the macrophages to increase the production of the cytokines. In addition, it is known that lactic acid bacteria increase the production of IL-12, IL-18, and TNF-α in antigens presenting cells such as dendritic cells often found in lymphatic nodes and mucosa of the digestive system. Furthermore, lactic acid bacteria are known to increase the expression of a surface molecule in dendritic cells that activate T lymphocytes such as MHC class II and B7-2 (Cross et. al., Anti-allergy properties of fermented foods: an important immunoregulatory mechanism of lactic acid bacteria?, International Immunopharmacology, Volume 1, May 2001, pages 891-901).
Much research on the interrelation between Lactobacillus sp. microorganisms and immune reactions has been carried out. Specifically, some Lactobacillus sp. (e.g. L. fermentum) is known to enhance an antigen-specific immune reaction, and thus its use as an adjuvant in bacteria (e.g. diphtheria, tetanus) or virus (e.g. influenza, polio) vaccines was tried (de Vrese et al., 2005; Olivares et al., 2007; West et al., 2008). Immune-enhancing effects of Lactobacillus sp. microorganism are considered to result from the enhanced activity of Th1-type cytokine-producing T lymphocyte by specific Lactobacillus sp. microorganisms, which effectively induce the growth of general immune cells and the activity of T cells or B cells in adaptive immunity (Mohamadzadeh et al., Lactobacilli activate human dendritic cells that skew T cells toward T helper 1 polarization, Proc Natl Acad Sci USA. 2005 22; 102(8):2880-2885). in order to measure the enhanced activity of T lymphocyte, the study of measuring the amount of produced IFN-γ is actively performed in recent years (Shida et al., 2006; Foligne et al., 2007). It is known that the induction of general immune cell growth may prevent or treat digestive tract (intestinal) infection (Jain S, Yadav H, Sinha P R. Probiotic dahi containing Lactobacillus casei protects against Salmonella enteritidis infection and modulates immune response in mice. J Med Food, 2009 June; 12(3):576-83.), genitourinary infection (Zarate G, Santos V, Nader-Macias M E. Protective effect of vaginal Lactobacillus paracasei CRL 1289 against urogenital infection produced by Staphylococcus aureus in a mouse animal model. Infect Dis Obstet Gynecol. 2009; 2009:48358. Epub 2007 Mar. 29.), respiratory infection (Yasuda Y, Matsumura Y, Kasahara K, Ouji N, Sugiura S. Mikasa K, Kita E. Microbial exposure early in life regulates airway inflammation in mice after infection with Streptococcus pneumoniae with enhancement of local resistance. Am J Physiol Lung Cell Mol Physiol. 2009 Sep. 25 [Epub ahead of print]), helicobacter infection (Boyanova L, Stephanova-Kondratenko M, Mitov I. Anti-Helicobacter pylori activity of Lactobacillus delbrueckii subsp. bulgaricus strains: preliminary report. Lett Appl Microbiol. 2009 May; 48(5):579-84. Epub 2009 Mar. 9.), and allergic reactions (Ouwehand A C, Nermes M, Collado M C. Rautonen N, Salminen S. Isolauri E. Specific probiotics alleviate allergic rhinitis during the birch pollen season. World 3 Gastroenterol. 2009 Jul. 14; 15(26):3261-8).
T lymphocytes control adaptive immunity which may be classified into a Th1 response as cellular immunity and a Th2 response as humoral immunity. Th1 and Th2 responses produce different cytokines in the antigen presenting cells. In the Th1 response, the production of IL-2, IL-12, IL-18, interferon-γ (IFN-γ is dominant. In the Th2 response, the production of PGE2, IL-4, and IL-10 is dominant. The Th1 and Th2 responses are required to be balanced. If the Th1 and Th2 responses are not balanced, a variety of immune diseases occur. Th1 cells mainly fight with pathogens, but Th2 cells are mainly related to allergies and inflammatory responses. When the Th1 and Th2 responses are in normal conditions, Th2 cells protect the human body from dust and undesired materials. However, if the Th2 cells excessively respond, the production of IgE antibodies increases, thereby causing allergic responses to proteins that are not hazardous to the human body, such as pollen and food. Thus, the ratio of Th1 and Th2 responses should be balanced. Excessive or insufficient response of one of them causes diseases. In addition, continuous secretion of cortisol due to continuous stress decreases Th1 response and increases Th2 response, thereby causing cancer, atopic diseases, allergies, and autoimmune diseases (Elenkov and Chrousos, Stress hormones, Th1/Th2 patterns, pro/anti-inflammatory cytokines and susceptibility to disease, Trends in Endocrinology and Metabolism, Volume 10, November 1999, pages 359-368).
According to in vivo experiments, lactic acid bacteria increase the production of IL-2 and IFN-γ that are Th1 cytokines in T lymphocytes and suppress the production of IL-4 and IL-5 that are Th2 cytokines (Matsuzaki et. al., The effect of oral feeding of Lactobacillus casei strain Shirota on immunoglobulin E production in mice, Journal of Dairy Science, Volume 81, January 1998, pages 48-53). Meanwhile, IL-12 and IL-18 are important cytokines to differentiate Th0 lymphocytes into Th1 lymphocytes and produced in macrophages or dendritic cells. It is known that the production of IL-12, IL-18 and IFN-α increases depending upon the concentration of lactic acid bacteria, when splenocytes or macrophages are treated with lactic acid bacteria during the culturing. As such, lactic acid bacteria increase the production of IL-12, IL-18 and IFN-α in macrophages, thereby promoting the differentiation of Th0 into Th1 and inducing the formation of IFN-γ and thus lactic acid bacteria play a role in balancing the Th1/Th2 in a Th2-response primed state (Cross et. al., Anti-allergy properties of fermented foods: an important immunoregulatory mechanism of lactic acid bacteria?, International Immunopharmacology, Volume 1, May 2001, pages 891-901). Thus, lactic acid bacteria are known to prevent and treat cancers, atopic diseases, allergies, and autoimmune diseases induced by the Th1/Th2 imbalance caused by the over-response of Th2.